PBTC Project Summary/Abstract The primary goal of the Pediatric Brain Tumor Consortium (PBTC) is to rapidly and effectively contribute to the understanding and cure of pediatric central nervous system (CNS) tumors through innovative, multidisciplinary and multi-institutional prospective clinical trials. PBTC clinical trial development is not only based upon known prognostic factors but also upon an evolving understanding of pediatric brain tumor biology. The PBTC will continue to utilize innovative study designs and analyses based on state-of-the-art statistical science. Novel clinical trials will incorporate relevant correlative pharmacology, biology, neuroimaging, immunologic and genomics studies in an effort to define and integrate these modalities into a better understanding of pediatric CNS tumors. These goals will be accomplished through a close and continued partnership with the member institutions' basic and translational scientists as well as the clinical trial experts. In addition, the PBTC welcomes partnerships with investigators outside the consortium providing scientific, laboratory and regulatory support for innovative and high priority clinical trials. The PBTC will continue to maintain and grow its relationship with the National Cancer Institute (NCI) and its large network of adult and pediatric groups as well as with pharmaceutical and biotechnology companies. One of the most important goals of the PBTC is to successfully complete focused phase I and II clinical trials of novel agents and treatment approaches that can be then be translated into large prospective phase II and III studies overseen by the Children's Oncology Group (COG). The overarching long-term goal is to improve survival outcome and quality of life for children with CNS tumor diagnoses that so often lead to high morbidity and mortality such as diffuse intrinsic pontine gliomas, high-grade gliomas, infant embryonal tumors, refractory medulloblastoma, ependymoma, and low-grade gliomas. To this end, the PBTC will continue to focus upon introducing novel molecularly-targeted agents via innovative trials to assess the presence of the target in tumor and surrogate tissue, evaluate the ability of the agent to down-regulate its signaling target and better correlate pharmacokinetic and pharmacodynamic endpoints with toxicities and clinical responses. The PBTC will also continue to explore therapeutic opportunities for pediatric brain tumors through immunotherapeutic interventions as well as via local delivery of treatments. By focusing on the most common solid tumor in children which also accounts for the highest number of cancer-related deaths in pediatrics, the PBTC will continue to support the NCI's mission of helping all people live longer, healthier lives through its contributions to cancer research and identification of better treatments.